Odashiro K, Hiramatsu S, Maruyama T, Kaji Y, Kanaya S, Fujino T, Niho Y
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Jpn Heart J. 1998 Jul;39(4):513-25. doi: 10.1536/ihj.39.513.
Since the mechanism of creatine kinase (CK) leakage induced by beta-adrenoceptor activation remains unclear, we studied the effects of incremental application (10(-9) to 10(-4) M) of isoproterenol (ISP) on the CK efflux from Langendorff-perfused isolated rat hearts under aerobic conditions. Tissue water content was estimated after the perfusion experiment. ISP-induced dose-dependent CK leakage was noted in a sigmoidal fashion, which showed low temperature-dependency (Q10 of 2.41), sensitivity to cepharantine (10(-6) M) and propranolol (10(-7) to 10(-6) M) without any signs of demand ischemia or oxidant stress. CK liberation was not replicated at all by maneuvers activating cAMP-dependent protein kinase (A-kinase). Myocardial edema noted in the control ISP application was ameliorated by exposure to 10(-6) M propranolol or cepharantine (i.e., significant fall in tissue water content; p < 0.05). Histological study revealed nonspecific myocardial fiber swelling and separation without any myocyte necrosis for all the perfusion groups. These results suggest that ISP-induced CK leakage in this model is not mediated by beta-adrenoceptor stimulation, subsequent A-kinase activation or related demand ischemia, but is attributed most to the direct effects of ISP augmenting sarcolemmal CK and water permeability.
由于β-肾上腺素受体激活诱导肌酸激酶（CK）泄漏的机制尚不清楚，我们研究了在有氧条件下，递增应用（10⁻⁹至10⁻⁴M）异丙肾上腺素（ISP）对Langendorff灌注的离体大鼠心脏CK流出的影响。灌注实验后估计组织含水量。观察到ISP诱导的CK泄漏呈剂量依赖性，呈S形曲线，显示出低温依赖性（Q10为2.41），对千金藤素（10⁻⁶M）和普萘洛尔（10⁻⁷至10⁻⁶M）敏感，且无任何需求性缺血或氧化应激迹象。激活cAMP依赖性蛋白激酶（A激酶）的操作完全不能复制CK的释放。在对照ISP应用中观察到的心肌水肿通过暴露于10⁻⁶M普萘洛尔或千金藤素而得到改善（即组织含水量显著下降；p<0.05）。组织学研究显示，所有灌注组均有非特异性心肌纤维肿胀和分离，但无任何心肌细胞坏死。这些结果表明，该模型中ISP诱导的CK泄漏不是由β-肾上腺素受体刺激、随后的A激酶激活或相关的需求性缺血介导的，而是主要归因于ISP增强肌膜CK和水通透性的直接作用。
